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Background: Post-stroke depression (PSD) has worse functional outcomes and quality of life. Despite the extensive literature on this topic, there is no agreement on the frequency or risk factors for post-stroke depression. Objectives: To establish the frequency and risk factors of post-stroke depression and its impact on quality of life. Patients and methods: One hundred three stroke patients were recruited from the out-patient clinic of Qena University Hospital who satisfied the WHO definition for stroke, together with a control group of 50 age- and sex-matched healthy volunteers. A complete history, neurological examination, and CT brain were obtained for each patient. DSM-IV TR criteria were used for diagnosis of depressive disorders which was scored with the Hamilton depression rating scale (HAM-D); Barthel Index (BI), and quality of life were also measured. Results: Thirty-eight (36.9%) stroke patients had PSD which was significantly higher than in the normal population (control group 12%). Statistically significant risk factors for PSD included low educational level, low socioeconomic status, smoking, and post-stroke functional impairment. Post-stroke depression has an impact on quality of life. Conclusion: Post-stroke depression is a relatively common complication of stroke and can affect the quality of life. Low educational level and socioeconomic status, as well as smoking and functional impairments, were considered as risk factors for the occurrence of post-stroke depression. Early detection of predictors of post-stroke depression may improve the outcome of stroke and prevent the psychiatric consequences. [ABSTRACT FROM AUTHOR]